Project Summary/Abstract: Immunology and Cancer Immunotherapy The Immunology and Cancer Immunotherapy (ICI) Program brings together 21 faculty, representing seven departments at Dartmouth?s Geisel School of Medicine (Geisel), its Thayer School of Engineering, and the Dartmouth-Hitchcock Health system (D-H), with research interests relevant to three central ICI Program themes: 1) Immune regulation and checkpoint blockade, 2) Tumor microenvironment, and 3) T cell immunology and CAR T therapy. The shared goals of the ICI Program are to: 1) drive translational immunology research, 2) explore fundamental mechanistic questions in tumor immunology, 3) make ground-breaking discoveries in cancer immunotherapy, and 4) initiate innovative immunotherapy clinical trials to study the underlying basis behind successful anti-tumor responses in humans. Peer-reviewed cancer-related research direct cost support currently totals $3.8M, with NCI funding representing 33% ($1.3M) and total direct costs summing to $4.8M. Ten ICI Program Members currently have a total of 12 CCSG-defined R01-equivalent awards. Using the same definition of cancer-related direct costs in 2014 (i.e., excluding all indirects as well as training and administrative direct costs), peer-reviewed cancer-related research direct costs ($3.8M) are 58% greater compared to 2014 ($2.4M). Since 2015, the ICI Program has 215 cancer-related publications, 21% (45) intra-programmatic, 29% (62) inter-programmatic, 54% (116) with investigators from other institutions, and 17% (32) in high impact journals (i.e., impact factor >8). Compared to 2014, intra-programmatic increased to 21% from 15%, and inter-programmatic has increased, to 29% from 24%. Major future goals include an immune checkpoint inhibitor research initiative to initiate an anti-VISTA clinical trial at NCCC, while continuing to uncover underlying mechanisms of drug efficacy in the laboratory; advancement of cutting-edge immunotherapy/molecular therapeutic combinations in clinical trials at NCCC, while extending collaborations with investigators in the newly created CBT program; a tumor microenvironment initiative to translate cowpea mosaic viral nanoparticle therapy from bench to bedside, in collaboration with the TEC program.; and, in memory T cell and CAR T cell therapy, to advance the engineering of T cells in preclinical work, including initiation of an NKG2D ligand-targeted CAR T cell clinical trial at NCCC.